Early Intensive Treatment Linked to Lower Risk of Death in Type 1 Diabetes

Early intensive treatment of type 1 diabetes is linked to a lower risk of death later in life compared with conventional therapy, according to data from approximately 27 years of followup in the randomized Diabetes Control and Complications Trial (DCCT) and the observational Epidemiology of Diabetes Control and Complications (EDIC) study. The findings were published in the January 6 issue of JAMA.

Dr. Aleppo's Commentary:

The findings of this important paper emphasize one specific word: early. It is important to treat these patients with type 1 aggressively and early, when they are either adolescent or young adults, or as soon as they are diagnosed if they are diagnosed in their 20s. This article reveals without a doubt how complications are a reality if blood glucose levels are not controlled early in life or in the first 10 years of the condition. Another important point is that, despite the fact that the intensive group cohort in EDIC had an increase of A1c from the target of 7% to about 8% after DCCT, there was still a significant decrease in mortality in the intensive group over many years of follow up.

To help patients with type 1 diabetes achieve tight glucose control, health care providers should take advantage of diabetes education. When these patients receive diabetes education early and with regular follow up, they are able to understand better how this condition affects their day-to-day glycemic fluctuations for many circumstances, such as exercise, sick days, etc. When these patients are trained early in their condition to recognize and count carbohydrates, they are able to more accurately take insulin for their meals and avoid overtreatment and undertreatment of their glucoses. The most important message to send to the health care providers is to embrace the latest technology to treat diabetes type 1, insulin pumps, and especially real time continuous glucose monitoring (CGM) systems, now that CGM sensors have become more accurate and reliable. CGM technology is the most important tool to achieve tight glycemic control without excessive hypoglycemia, because it informs the patient of the glucose trends and patterns and alerts them of impending hypoglycemia, which has been historically the main obstacle to tight glycemic control in this population.

The most recent guidelines for glycemic control in the diabetic pediatrics population has set lower goals for A1c levels, and they reflect an effort to focus on early intensive treatment for type 1 diabetes. In the next several years, hopefully we will be able to see the effects of these new targets, undoubtedly with the help of tools such as insulin pumps, CGMs, and pumps with threshold suspend features.

About the Study"These results should remove any lingering doubts about the safety of intensive therapy in terms of fatal hypoglycemia and provide further data to support adoption of intensive therapy in the young adolescent/adult with type 1 diabetes," said lead author Trevor Orchard MD, Professor of Epidemiology, Medicine, and Pediatrics at the University of Pittsburgh Graduate School of Public Health.

In addition, the findings "complete our knowledge about the benefits of intensive therapy of type 1 diabetes designed to get the hemoglobin A1c to or below 7%. We have previously shown that this dramatically reduces the chances of developing eye, nerve, kidney and heart disease, and now it has been shown to reduce early mortality," Dr. Orchard said. "Taken with other data it now seems most individuals with type 1 diabetes can expect a normal life expectancy," he added.

DCCT Findings
In the DCCT, which was conducted from 1983 to 1993, 1,441 healthy volunteers with type 1 diabetes mellitus (ages 13 to 39 years at baseline) were randomized to intensive therapy designed to established near-normal glycemic levels, or conventional therapy designed to avoid symptomatic hypoglycemia and hyperglycemia. At baseline, the patients' duration of diabetes ranged from 1 to 15 years; patients had no or early microvascular complications, and patients did not have hypertension, preexisting cardiovascular disease, or other potentially life-threatening disease. Mean hemoglobin A1c levels during the study were 7% and 9% in the intensive and conventional therapy groups, respectively.

After a mean follow-up of 6.5 years, patients randomized to intensive therapy showed significantly lower incidences of retinopathy, albuminuria, and neuropathy compared with the conventional group. At the end of the study, the intensive therapy group was encouraged to continue intensive therapy practices, and the conventional group was taught intensive therapy.

EDIC Findings
A total of 1,394 of the DCCT participants were followed up in the observational EDIC study from 1994 to 2012. After 5 years of follow-up in the EDIC, the two groups showed no statistically significant difference in blood glucose control (A1c was approximately 8% in both groups).

Mortality Rate Was 33% Lower in the Intensive Treatment Group
In the current analysis of DCCT/EDIC participants who were followed for an average of 27 years from enrollment, 107 deaths occurred—43 (40.2%) in the group that originally received intensive treatment and 64 (59.8%) in the group that originally received conventional treatment, which translated into a 33% reduced risk of death. The difference in mortality did not emerge between the study groups until 15 years of follow-up.

The most common causes of death were cardiovascular disease (22%), cancer (20%), acute diabetes complications (ie, hyperglycemia or hypoglycemia; 18%), and accidents/suicide (17%). More people in the conventional treatment group than in the intervention group died from diabetic kidney disease (6 vs. 1), cardiovascular disease (15 vs. 9), and cancer (14 vs. 7).

The mortality risk was significantly higher in patients with higher A1c levels (hazard ratio=1.56; P<0.01) and among patients with albuminuria (hazard ratio=2.20; P<0.01).

"These results build on earlier studies, which suggested that increased protein in the urine largely accounts for shorter lifespans for people with type 1 diabetes," said Dr. Orchard. "These results further emphasize the importance of good early glucose control, as this reduces the risk for increased protein in the urine in general, as well as diabetic kidney disease," Dr. Orchard said.

"Important though these results are, individuals also should keep their blood pressure and blood fats under control!," Dr. Orchard added.

February 12, 2015

View Sources

Writing Group for the DCCT/EDIC Research Group, Orchard TJ, Nathan DM, et al. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 2015;313(1):45-53.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329(14):977-986.

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